One mechanism that has been suggested for chemical induction of cancer is the binding of a species of the carcinogen to a cellular macromolecule, particularly DNA. A limitation in previous experiments designed to show this binding has been the necessity of extensively purifying these macromolecules in order to identify the adducts. It is possible that the most persistent and stable adducts are not the most important in chemical carcinogenesis and that the less stable adducts do not survive the harsh chemical methods required for isolation. Moreover, the sensitivity of present analytical methods prevents direct identification of the carcinogen-macromolecule complex. We propose to use a powerful new spectroscopic technique, Optical Detection of Magnetic Resonance, to investigate carcinogen binding. The advantages of this method include an increased order of sensitivity, the capacity to identify the bound carcinogen or its metabolite(s) in situ, and the ability to use optically opaque material--including cell homogenates and possibly even cells themselves--for analysis. We propose to carry out preliminary experiments to test this analytical technique with model systems including macromolecular complexes with acetylaminofluorene and with aflatoxin and their derivatives, to identify the bound metabolite(s), and to identify the products released in the course of chemical isolation. With these data, an attempt will be made to characterize the interaction of these carcinogens during acute and chronic exposure in rodents. We wish to test the hypothesis that carcinogen binding is necessary for cell transformation, that specific sites are involved and that this binding is covalent. Should the promise of this approach be realized, then a new method would be at hand for investigating chemical modifications of cellular macromolecules during carcinogenesis and to designate the specific type and locus of the binding.